The present invention is related to methods and apparatus for treating arrhythmias such as atrial and/or ventricular fibrillation in subjects.
The heart is a muscular organ which is covered by a fibrous sac known as the pericardium. The space between the pericardium and the muscular organ is called the pericardial space. The walls of the heart are substantially formed from muscle (the myocardium) which differs from either skeletal or smooth muscle. The heart comprises atria and ventricles, each of which is composed of layers of myocardium which are formed to encase the blood-filled chambers. In operation, when the walls of a chamber contract, they come together similar to a squeezing fist. This contraction of the cardiac muscle is triggered by depolarization of the muscle membrane. To operate properly, the muscle contractions should be coordinated.
If the muscle contractions are not coordinated within the ventricles, blood may be sloshed back and forth within the ventricular cavities instead of being ejected into the aorta and pulmonary arteries. Thus, the complex muscle masses forming the ventricular pumps should contract substantially simultaneously for efficient pumping.
The heart is able to achieve this coordination because of (a) the tight junctions formed between adjacent cardiac fibers (the fibers are joined end to end at structures known as intercalated disks, which provide the points or junctions) which allow action potentials to be transmitted from one cardiac cell to another; and (b) the specialized muscle fibers in certain areas of the heart which provide the conducting system for proper excitation of the heart. The specialized fibers are in contact with fibers of the cardiac muscles to form gap junctions, which permit passage of action potentials from one cell to another. The specialized conduction system is configured, in normal operation, to provide a rapid and coordinated spread of excitation.
Cardiac muscle cells are autorhythmic, i.e., capable of spontaneous, rhythmical self-excitation. The sinoatrial (SA) node is the normal pacemaker for the entire heart or smooth muscle, and it is from this region that the excitation wave starts; it then moves or propagates through the remainder of the myocardium in a synchronized manner. The SA node region of the heart contains a small mass of specialized myocardial cells in the right atrial wall near the entrance of the superior vena cava which have a fast inherent rhythm, which allows the SA node to be the normal pacemaker. In unusual circumstances, other regions of the heart can become more excitable and provide a faster spontaneous rhythm. In this situation, this other region can become the pacemaker and the rhythm for the entire heart.
In normal operation, the cells of the SA node make contact with the surrounding atrial myocardium fibers. Thus, from the SA node, a wave of excitation spreads throughout the right atrium along the atrial myocardial cells via the gap junctions. In addition, the specialized conducting system directs the impulse from the SA node directly to the left atrium, to simultaneously contract both atria.
The excitation wave then is distributed to the ventricles by way of a second small mass of specialized cells located at the base of the right atrium near the wall between the ventricles (the atrioventricular (AV) node). The AV node is configured to delay the propagation of action potentials (the wavefront) by about 0.1 second, to allow the atria to contract and empty the blood into the ventricle before ventricular contraction. The wavefront is then quickly dispersed along the specialized conducting fibers (down the interventricular septum) and then through unspecialized (typical) myocardial fibers in the remaining myocardium.
The pumping of blood includes alternate periods of contraction and relaxation. The cardiac muscle has a relatively long refractory period (on the order of about 250 ms). This refractory period is a time during which the membrane is insensitive to stimulus (either totally unable to propagate an excitation wave or only able to do so upon exposure to an increased level of stimulation).
During ventricullar fibrillation (VF) a number of independent activation wavefronts propagate simultaneously through the mycodardium. It has been suggested that as soon as the myocardium becomes excitable, it is excited by a wandering wavefront. See Lammers et al., The use of fibrillation cycle length to determine spatial dispersion in eletrophysiologic properties used to characterize the underlying mechanism of fibrillation, 2 N. Trends Arrhythmia, pp. 109-112 (1986); Opthof, et al., Dispersion of refracteries in canine ventricular myocardium: Effects of sympathetic stimulation, 68 Circ. Res., pp. 1204-1215 (1991). This proposition would indicate that there is no excitable gap between activations and would preclude the possibility of capturing fibrillation with exogenously generated electrical stimuli. However, pacing stimuli have been shown to be able to capture the myocardium during fibrillation. For example, Allesie et al and Kirchhof et al. report successful pacing of the canine left atrium during atrial fibrillation; and Daoud et al. and Capucci et al. report successful pacing of the human right atrium during atrial fibrillation. Others report pacing of right ventricular free wall during VF, although capture of the fibrillating myocardium was only successful in about 36% of the episodes. See KenKnight et al., Regional capture of fibrillating ventricular myocardium: Evidence of an excitable gap, 77 Circ. Res. 849-855 (1995). In addition, in the past, the amount of myocardium captured by pacing via a single electrode has been relatively modest.
The present invention provides improved methods and devices for pacing the heart by increasing the number of pacing sites. Certain embodiments of the pacing systems of the present invention include a plurality of discrete electrodes, a single elongated electrode, or one or more line electrodes, arranged to direct at least one pacing train to multiple sites within a selected localized region or regions of the myocardium during a treatment window such as during an episodic onset of an arrhythmia or during a fibrillating event (whether in the atria, the ventricles, or both). In certain embodiments, the present invention can provide a plurality of pacing trains which transmit stimulation pulses to multiple proximately located sites in the myocardium at the time of the onset of a sensed or detected arrhythmia or fibrillation event. In certain embodiments, the timing and/or strength of the pacing trains and the position of the electrodes which transmit the stimuli may improve the likelihood that the arrhythmia will be halted and/or that fibrillating myocardium will be captured.
The pacing train stimuli can be configured with sufficient strength to control the excitation of the heart in the region undergoing stimulation. In certain embodiments, the pacing trains are sequentially delivered and each has an increased electrical strength (increased current) which is well above the lowest electrical stimulation needed to excite the myocardium in the region of interest during diastole of paced or sinus rhythm. In some embodiments, a diastolic pacing threshold (DPT) can be predetermined in situ (DPT is the lowest strength which is able activate the tissue during diastole of paced or sinus rhythm) and for pacing, a 5xc3x97-10xc3x97DPT stimulation strength can be employed.
Certain embodiments of the present invention are configured, by electrode placement and/or the selection of pacing signals, so that at least a 30-40 mm2 region proximate the stimulus per pacing cycle may be captured, and typically the captured area is between 40 mm2-200 mm2 and higher (such as about 500 mm2, or even up to about the area of substantially the entire myocardium).
One aspect of the invention is a method of pacing to treat arrhythmia in a patient, comprising the steps of: (a) positioning at least one line electrode in a localized region of the heart of a patient such that it covers multiple pacing sites over a distance of between about 0.25-15 cm; and (b) delivering a first pacing stimulation pulse train comprising a plurality of excitation pulses to the at least one electrode to the corresponding multiple pacing sites to pace the myocardium of the patient.
In some embodiments, the first pacing train is delivered responsive to the onset of a fibrillation event. The method can also include the step of delivering a second and/or third pacing train comprising a plurality of excitation pulses to the plurality of sites after the first delivering step. In other embodiments, the method can include the step of administering a pharmacological agent to the patient to increase the degree of organization and/or the step of delivering a defibrillation shock pulse to the patient proximate in time to (including before or during) the fibrillation event. In addition, or alternatively, a defibrillation pulse can also be delivered after pacing and/or with a pharmacological agent.
The present invention may also sense cardiac activity so as to adjust one or more of the pacing stimulation parameters of the pacing stimulation pulse (such as duration, strength, rate, and the like). The sensing information may also be used to delay the delivery of the stimulation until a desired degree of organization is indicated (such as a degree of regularity of cycle intervals).
The present invention can provide a pacing system for the heart of a subject which includes a pulse generator configured to generate at least one, and in at least some embodiments, a plurality of pacing trains, each pacing train having a plurality of stimulation pulses; a power source operably associated with the pulse generator; and at least one electrode configured to pace over multiple sites in one or more localized regions of the myocardium (such as an elongated line electrode or a plurality of electrodes) operably associated with the pulse generator and adapted, in operation, to reside about a localized region of the myocardium so as to be able to pace over multiple pacing sites. The electrodes may be carried on a catheter of mounted on a lead wire and positioned at the desired target region in the heart. The system may also include a detector to sense various cardiac activity such as the onset of an irregular cardiac condition (and/or the intrinsic pacing cycle). The electrodes can be configured to operate with increased resistivity (to be equal to or greater than the resistivity of the myocardium). This may include resistance added in series or parallel arrangements between the pulse generator and the electrode to help balance or reduce the edge effects of the electrode arrangement.
In certain embodiments, the plurality of electrodes can be arranged on one or more line electrodes and the electrodes can be arranged to transmit the pacing train stimuli to the myocardium at the prospective contact points at different sites substantially concurrently. In some embodiments, the electrodes can be configured to transmit the pacing train stimuli in operative spaced apart electrode pairs. The electrodes can be held on two substantially parallel spaced apart line electrodes positioned in at least one localized region of the heart so that the electrodes contact the myocardium. Using two or more electrode pairs (in spaced apart proximity so as to be able to act together to limit reentry circuits) may increase the amount of capture area over that attributed to two electrode systems acting apart.
Another pacing system for the heart of a subject is similar to the one described above, but the electrode can be configured as a line electrode having a contiguous or solid body elongated electrode having a length of between about 0.25-15 cm (and more typically above about 0.5-1 cm to about 15 cm) adapted, in operation, to reside about a localized region of the myocardium.
Another aspect of the invention is a pacing stimulation pulse sequence, comprising a first pacing train having a plurality of excitation pulses at an electrical strength of between about 5-10xc3x97DPT; and a second pacing train having a plurality of excitation pulses at an electrical strength of between about 5-10xc3x97DPT. The first and second pacing trains are transmitted to a region of the myocardium to pace the excitation of the heart. The pacing stimulation can be transmitted to portions of myocardium where the refractory period is short or the defibrillation shock has a weak effect and/or including sites of ventricular fibrillation (VF) maintenance such as rotors reentrant loops, and sites of focal activity.
The present invention now allows pacing from several proximate sites (via multiple contact points) within a localized region or regions, alone, or in conjunction with the delivery of a defibrillation shock to treat fibrillation. To treat atrial or ventricular fibrillation, the pacing train stimuli may be sized and delivered to the myocardium in a manner which can capture sufficient tissue such that substantially all reentrant circuits capable of maintaining fibrillation are eliminated thereby potentially eliminating the need for the use of defibrillation shocks under some conditions.
Multi-site pacing (via one or more contiguous body (line) electrodes or a plurality of adjacently aligned electrodes) may also be used with the administration of pharmacological agents to increase the degree of organization so that pacing can capture larger regions or so that the number of reentrant circuits is reduced. It is also anticipated that pacing during fibrillation may be combined with conventional defibrillation techniques so that a lower strength shock can be used to defibrillate. This may be accomplished by pacing in areas of myocardium where the defibrillation shock has its weakest effect. It is anticipated that pacing may control activation in this area so that it stops with the termination of pacing, and, thus, the shock strength can be decreased to a strength needed to halt fibrillation in the remaining portions of the myocardium not captured by pacing. This technique may synchronize these defibrillation shocks with respect to the pacing so that the defibrillation shock itself does not re-induce fibrillation in the region captured by pacing. These types of defibrillation treatment methods may be particularly suitable for atrial fibrillation, because they may be able to reduce the discomfort associated with the strong shocks conventionally needed to halt the atrial fibrillation.
The foregoing and other objects and aspects of the present invention are explained in detail in the specification set forth below.